BACKGROUND: The liver, as the main iron storage compartment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Excessive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases.

DATA SOURCES: PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease progression. We have also included literature on adjuvant therapeutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis.

RESULTS: Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identification of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause significant improvement of liver functions in patients with iron overload. Phlebotomy can have beneficial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology.

CONCLUSION: Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and available data suggest that it can be considered as target for adjuvant therapy in this condition.

 METHODS: One hundred thirty-one consecutive adult patients who underwent orthotopic liver transplantation from DCD were retrospectively studied. Based on serum potassium within 5 minutes after reperfusion, recipients were divided into two groups: hyperkalemia and normokalemia. According to preoperative biopsy results, the DCD graft livers were classified into five categories. Univariate analysis was performed using Chi-square test to identify variables that were significantly different between two groups. Multivariate logistic regression was used to confirm the risk factors of developing hyperkalemia and postreperfusion syndrome. Correlation analysis was used to identify the relationship between the serum concentration of potassium within 5 minutes after reperfusion and the difference in mean arterial pressure values before and within 5 minutes after reperfusion.

RESULTS: Twenty-two of 131 liver recipients had hyperkalemia episodes within 5 minutes after reperfusion. The rate of hyperkalemia was significantly higher in recipients of macrosteatotic DCD graft liver (78.6%, P<0.001) than that in recipients of non-macrosteatotic DCD graft liver. The odds ratio of developing postreperfusion hyperkalemia in recipients of macrosteatotic DCD graft liver was 51.3 (P<0.001). Macrosteatosis in the DCD graft liver was an independent risk factor of developing hyperkalemia within 5 minutes after reperfusion. The highest rate of postreperfusion syndrome also occurred in the recipients with macrosteatotic DCD graft liver (71.4%, P<0.001). A strong relationship existed between the serum potassium within 5 minutes after reperfusion and the difference in mean arterial pressure values before and within 5 minutes after reperfusion in macrosteatotic DCD graft liver recipients.

CONCLUSION: Macrosteatosis in the DCD graft liver was an independent risk factor of developing hyperkalemia and postreperfusion syndrome in the recipients.

BACKGROUND: Chemoembolization with doxorubucin-eluting beads (DEB) has been used to treat hepatocellular carcinoma (HCC) since 2007. This study compared the efficacy and survival between transarterial chemoembolization (TACE) with DEB and conventional approach (cTACE) in HCC treatment.

METHODS: This retrospective case-control study compared the overall survival and tumor response of HCC patients to cTACE (n=190) and DEB (n=143) by the reassessment of computed tomography and serum alpha-fetoprotein (AFP). Multivariate analysis was used to determine the factors affecting tumor response.

RESULTS: The median post-treatment to pre-treatment AFP level was 0.8 for a DEB session (n=258) and 1.0 for a cTACE session (n=452), showing a significantly greater decrease in AFP after DEB (P<0.05). More patients in the DEB group achieved objective response (complete and partial) compared with those in the cTACE group (P<0.05). Objective tumor response after DEB vs cTACE was 34.8% vs 15.4% in 0-3 months (P=0.001), 37.1% vs 20.0% in 3-6 months (P<0.05), and 50.0% vs 30.0% in 6-12 months (P=0.093). DEB predicted a 3.604 times odds of achieving at least one objective tumor response in a patient when compared to cTACE (P<0.0001). The median survival from first transcatheter therapy of patients having undergone at least once DEB was 12.53 months, while those having received cTACE only was 10.53 months (P=0.086). A tendency of improved survival appeared to maintain until >80 months after the first TACE session in the DEB group.

CONCLUSION: DEB is a safe alternative to cTACE in HCC patients with better therapeutic efficacy.

BACKGROUND: Portal vein thrombosis (PVT) is due to many risk factors, but its pathogenesis is still not clearly understood. To identify the risk factors for PVT, we analyzed the clinical characteristics and complications associated with PVT in cirrhotic patients.

METHODS: We studied patients with liver cirrhosis who were admitted to our unit from April 2009 to December 2014. The patients were divided into the PVT and non-PVT groups, and were compared by variables including gender, age, the etiology of cirrhosis, stage of cirrhosis, complications, imaging, and treatment.

RESULTS: PVT was found in 45 (9.8%) of 461 cirrhotic patients admitted to our hospital. Most patients (45.9%) had hepatitis B virus (HBV)-related cirrhosis, with a similar distribution of etiologies between the groups. However, there was no positive relationship between PVT and etiologies of cirrhosis. Most patients (71.5%) were in the stage of hepatic decompensation. No statistically significant differences were found in complications including esophageal varices, ascites, and hepatic encephalopathy between the groups. However, there was a significant positive correlation between hepatocellular carcinoma (HCC) and PVT (P<0.01). In 30 patients with PVT, thrombosis occurred in the portal vein and/or portal branches, 37.8% were diagnosed on ultrasound.

CONCLUSIONS: The incidence of PVT was 9.8%, mainly in patients with HBV-related cirrhosis. The development of PVT was associated with the severity of liver disease and HCC.

BACKGROUND: Etiologic organism is not frequently isolated despite multiple blood and fluid cultures during management of pyogenic liver abscess (PLA). Such culture negative pyogenic liver abscess (CNPLA) is routinely managed by antibiotics targeted to Klebsiella pneumoniae. In this study, we evaluated the outcomes of such clinical practice.

METHODS: All the patients with CNPLA and Klebsiella pneumoniae PLA (KPPLA) admitted from January 2003 to December 2011 were included in the study. A retrospective review of medical records was performed and demographic, clinical and outcome data were collected.

RESULTS: A total of 528 patients were treated as CNPLA or KPPLA over the study period. CNPLA presented more commonly with abdominal pain (P=0.024). KPPLA was more common in older age (P=0.029) and was associated with thrombocytopenia (P=0.001), elevated creatinine (P=0.002), bilirubin (P=0.001), alanine aminotransferase (P=0.006) and C-reactive protein level (P=0.036). CNPLA patients tend to have anemia (P=0.015) and smaller abscess (P=0.008). There was no difference in hospital stay (15.7 vs 16.8 days) or mortality (14.0% vs 11.0%). No patients required surgical drainage after initiation of medical therapy.

CONCLUSION: Despite demographic and clinical differences between CNPLA and KPPLA, overall outcomes are not different.

BACKGROUND: Ischemia reperfusion injury (IRI) is unavoidable in liver transplantation and hepatectomy. The present study aimed to explore the possible mechanism and the effect of oleanolic acid (OA) in hepatic IRI.

METHODS: Mice were randomly divided into 6 groups based on different treatment. IRI model: The hepatic artery, portal vein, and bile duct to the left and median liver lobes (70% of the liver) were occluded with an atraumatic bulldog clamp for 90 minutes and then the clamp was removed for reperfusion. The mice were sacrificed 6 hours after reperfusion, and blood and liver tissues were collected. Liver injury was evaluated by biochemical and histopathologic examinations. The expressions of Sesn2, PI3K, Akt and heme oxygenase-1 (HO-1) were measured with quantitative real-time RT-PCR and Western blotting.

RESULTS: The serum aminotransferases level and scores of hepatic histology were increased after reperfusion. The increase was attenuated by pretreatment with OA (P<0.01). Compared with the IR group, OA pretreatment significantly up-regulated the expression of Sesn2, PI3K, Akt and HO-1 in IR livers (P<0.05). Administration of zinc protoporphyrin (ZnPP), an inhibitor of HO-1, diminished the OA effect on HO-1 and Sesn2 expressions (P<0.05) and the protective effect of OA on IRI.

CONCLUSIONS: Our results demonstrate that OA can attenuate hepatic IRI. The protective mechanism may be related to the OA-induced HO-1/Sesn2 signaling pathway.

BACKGROUND: This study aimed to compare the rates of open and laparoscopic cholecystectomies and outcomes in patients with or without type 2 diabetes mellitus (T2DM) in Spain from 2003 to 2013.

METHODS: We collected all cases of open and laparoscopic cholecystectomies using national hospital discharge data and evaluated the annual cholecystectomy rates stratified by T2DM status. We analyzed tendency for in-hospital mortality (IHM). We also analyzed the impact of T2DM on IHM in patients who underwent cholecystectomies.

RESULTS: We identified 611 533 cholecystectomies (71.3% laparoscopic) in the patients, in whom 78 227 (12.8%) patients had T2DM. The rates of open cholecystectomies were 3-fold higher (130.0/105 vs 41.1/105) in patients with T2DM than in those without T2DM, and the rate of laparoscopic cholecystectomies was almost 2-fold higher (195.2/105 vs 111.8/105) in patients with T2DM. The annual rate of laparoscopic procedures showed an 11-year relative increase of 88.3% (from 117.0/105 to 220.3/105) in T2DM and 49.2% (from 79.2/105 to 118.2/105) in patients without T2DM (P<0.001), whereas the rate of open procedures showed an 11-year relative decrease of 27.6% in patients with T2DM and 37.9% in those without T2DM (P<0.001). The rate of emergency laparoscopic cholecystectomy was increased in the 11 years, whereas the rate of emergency open cholecystectomies was decreased (both P<0.001). Multivariate analysis revealed that older age, higher comorbidity and emergency cholecystectomy were associated with a higher IHM. Compared with patients without T2DM, patients with T2DM demonstrated a lower IHM after open cholecystectomy [OR=0.82 (0.78-0.87)], but a higher IHM after laparoscopic cholecystectomy [OR=1.18 (1.03-1.35)]. Time-trend analyses showed a significant reduction in IHM in patients with or without T2DM after the two procedures.

CONCLUSION: The rate of cholecystectomy was higher in patients with T2DM, and laparoscopic cholecystectomy was popularized in the past 11 years both in selective and emergency cholecystectomies.

BACKGROUND: The frequency of isolated biliary candidiasis is increasing in cancer patients. The clinical significance of isolated biliary candidiasis remains unclear. We analyzed the risk factors of biliary candidiasis and outcomes of the patients with unresectable cholangiocarcinoma after percutaneous transhepatic biliary drainage (PTBD).

METHODS: Among 430 patients who underwent PTBD between January 2012 and March 2015, 121 patients had unresectable cholangiocarcinoma. Bile and blood samples were collected for consecutive fungal culture.

RESULTS: The study cohort included 49 women and 72 men with a median age of 71 years. Multivariate analysis showed that cancer progression (P=0.013), concurrent presence of another microorganism (P=0.010), and previous long-term (>7 days) antibiotic use (P=0.011) were potential risk factors of biliary candidiasis. Chemotherapy was not associated with overall biliary candidiasis (P=0.196), but was significantly related to repeated biliary candidiasis (P=0.011). Patients with isolated biliary candidiasis showed remarkably reduced survival compared with those without [median overall survival (OS): 32 vs 62 days, P=0.011]. Subgroup analysis was also performed. Patients with repeated candidiasis had markedly decreased survival compared with those with transient candidiasis (median OS: 30 vs 49 days, P=0.046). Biliary candidiasis was identified as a poor prognostic factor by univariate and multivariate analyses (P=0.033). Four cases of repeated candidiasis (4/19, 21%) showed Candida species in consecutive blood culture until the end of the study, but others showed no candidemia.

CONCLUSIONS: Isolated biliary candidiasis may be associated with poor prognosis in patients with unresectable cholangiocarcinoma. Especially, repeated biliary candidiasis may have the possibility of progression to candidemia. We suggest that biliary dilatation treatment or antifungal agents might be helpful for patients with biliary candidiasis.

BACKGROUND: Ultrasound-guided transversus abdominis plane (TAP) block is an adjunct therapy to provide effective postoperative analgesia in abdominal surgical procedures. Dexamethasone is a supplement agent that can improve the efficacy of local anesthesia. However, information about its additive effect is limited. This study aimed to compare the analgesic efficiency using ultrasound-guided TAP block with and without perineural dexamethasone for patients who underwent laparoscopic cholecystectomy.

METHODS: Sixty patients who underwent laparoscopic cholecystectomy were randomly divided into three groups: group I, controls; group II, TAP; and group III, TAP+perineural dexamethasone supplement. The requirement of additional analgesia and the first-time request of rescue-analgesia were recorded after operation and the numerical rating scale was evaluated at specific intervals.

RESULTS: Compared to group I, the first-time requirement of rescue-analgesia in groups II and III was significantly delayed (403.0±230.9, 436.0±225.3 vs 152.3±124.7, P<0.01). Compared with those in group I, patients in groups II and III were associated with lower numerical rating scale pain scores (P<0.01) and less postoperative analgesic consumption (P<0.01). There was no significant difference in the variables mentioned above between groups II and III (P>0.05).

CONCLUSION: Perineural dexamethasone has no additive/synergistic effect with subcostal TAP block on analgesic efficacy for the patients undergoing laparoscopic cholecystectomy.

BACKGROUND: Fast track strategy in the management of patients undergoing intra-abdominal surgery of various types has emerged as a landmark approach to reduce surgical stress and accelerate recovery. This study was to evaluate the effect of fast track strategy on patients subjected to pancreaticoduodenectomy (PD) from an individual unit during transit from low to a high volume center.

METHODS: A total of 142 PD patients who had been subjected to fast track strategy between June 2008 and September 2012 were compared with 46 patients who had received conventional surgery between January 2006 and May 2008. Comparative analysis was made of postoperative complications, postoperative recovery, length of hospital stay and patient readmission requirement.

RESULTS: The patients subjected to fast track strategy had a faster recovery and a shorter hospital stay than those who were treated conventionally (7.8 vs 12.1 days). The intraoperative events like operative blood loss (417.9±83.8 vs 997.4±151.8 mL, P<0.001), blood transfused (a median of 0 vs 1 unit, P<0.001) and operative time taken (125 vs 245 minutes, P<0.001) were significantly lower in the fast track group. The frequency of pancreatic fistula (4.9% vs 13.0%) and delayed gastric emptying (7.0% vs 17.4%) was also significantly reduced with fast track treatment. Nevertheless, the readmission rate (11.3% vs 6.5%) was found relatively higher within the fast track group. However, increased readmission rates in this study seem to be independent of fast track protocol.

CONCLUSIONS: This preliminary analysis suggests that the fast track approach might be beneficial to the well-being of the patients after PD, for it accelerates the immediate clinical recovery of patients and significantly shortens their length of hospital stay.

BACKGROUND: Serum cancer antigen 19-9 (CA19-9) provides additional information about mucinous cystic pancreatic neoplasm (MPN). This study was undertaken to assess both CA19-9 and carcinoembryonic antigen (CEA) serum concentrations in consecutive patients affected by MPNs and other chronic benign and malignant pancreatic diseases. We also evaluated whether serum CA19-9 and CEA determinations provide additional information such as the presence of invasive carcinoma in MPN patients.

METHODS: Serum CA19-9 and CEA from 91 patients with pancreatic diseases were tested by commercially available kits at the time of diagnosis. The upper reference limit of serum CA19-9 was 37 U/mL and that of serum CEA was 3 ng/mL.

RESULTS: Thirty-five patients was diagnosed with chronic pancreatitis (CP), 32 with MPN, and 24 with pancreatic ductal adenocarcinoma (PDAC) confirmed histologically. Surgery was carried out in 5 CP patients, in 10 MPN patients (7 of them had severe dysplasia), and 9 PDAC patients. Serum CA19-9 activity was high in 12 (34.3%) CP patients, in 7 (21.9%) MPN patients, and in 12 (50.0%) PDAC patients (P=0.089). High serum CEA concentrations were noted in 6 (17.1%) CP patients, in 6 (18.8%) MPN patients, and in 12 (50.0%) PDAC patients (P=0.010). In the 7 MPN patients associated with histologically confirmed severe dysplasia, 3 (42.9%) patients had elevated serum activity of serum CA19-9, and 2 (28.6%) patients had high levels of CEA.

CONCLUSION: Serum determination of oncological markers is not useful in selecting MPN patients with malignant changes.